Arena issued metabolic screening patent

"The invention set forth in this patent has been instrumental in identifying G Protein-Coupled Receptor targeted compounds that have the potential to regulate plasma lipid profiles, including HDL cholesterol, similar to the therapeutic action of niacin,"​ commented Jack Lief, Arena's president and chief executive officer. "Utilising the technology in this patent, our cardiovascular disease collaboration with Merck is making progress towards its goal of discovering a drug with improved characteristics over today's treatments."​

Drugs that can influence the levels of LDL and HDL cholesterol may potentially provide clinical benefits to patients by reducing the risk of heart attack and stroke.

Blood contains two types cholesterol: LDL and HDL cholesterol. Generally, LDL is considered the "bad cholesterol" because it can leave deposits inside the walls of blood vessels, which can adversely effect blood flow and over time increase the risk of heart attack and stroke.

HDL cholesterol, considered the "good cholesterol," can help clear the "bad" deposits caused by LDL cholesterol by removing them from the walls of blood vessels and transporting them to the liver for processing and removal from the body.

The patent, entitled: "Human G Protein-Coupled Receptors and Modulators Thereof for the Treatment of Metabolic-Related Disorders," is instrumental in identifying G Protein-Coupled Receptor targeted compounds that have the potential to regulate plasma lipid profiles.

Although a number of receptor classes exist in humans, by far the most therapeutically relevant is represented by the G protein-coupled receptor (GPCR) class. It is estimated that there are some 3 billion genes within the human genome, and of these, approximately 2 per cent are estimated to code for GPCRs.

Receptors, including GPCRs, for which the endogenous ligand has been identified, are referred to as "known" receptors, while receptors for which the endogenous ligand has not been identified are referred to as "orphan" receptors.

GPCRs represent an important area for the development of pharmaceutical products: from approximately 20 of the 100 known GPCRs, approximately 60 per cent of all prescription pharmaceuticals have been developed.

Pharmaceutical drugs that target GPCR include Claritin, used for allergies, Paxil, for depression, and Vasotec for hypertension.

Atherosclerosis and stroke are the numbers one and number three leading causes of death of both men and women in the United States. Type 2 diabetes is a public health problem that is serious, widespread and increasing

Elevated levels of low-density lipoprotein (LDL) cholesterol or low levels of high-density lipoprotein (HDL) cholesterol are, independently, risk factors for atherosclerosis and associated cardiovascular pathologies. In addition, high levels of plasma free fatty acids are associated with insulin resistance and type 2 diabetes.

One strategy for decreasing LDL-cholesterol, increasing HDL-cholesterol, and decreasing plasma free fatty acids is to inhibit lipolysis in adipose tissue. This approach involves regulation of hormone sensitive lipase, which is the rate-limiting enzyme in lipolysis. Lipolytic agents increase cellular levels of cAMP, which leads to activation of hormone sensitive lipase within adipocytes. Agents that lower intracellular cAMP levels, by contrast, would be antilipolytic.

In October 2002, Arena​ entered into a research and licensing agreement with Merck to collaborate on three GPCRs to develop therapeutics for atherosclerosis and related disorders. This was followed up in October 2004, where Merck extended and expanded the collaboration selecting one of Arena's compounds for preclinical development.

As a sign of the success of the collaboration, Arena have received research funding from Merck, who have agreed to pay $5.7 million a year for collaboration research through to October 2007.